Start Strong, Scale Fast: Reframing Process Chemistry in Preclinical Drug Discovery

There’s a persistent belief in drug development circles that process chemistry starts when clinical trials begin. That until you’re ready to produce GMP material at a CDMO, there’s little need to think about routes, scale, or robustness. Even at this stage not everything must be GMP! It’s a misconception we’ve seen cost programs both time and money, and in some cases, derail them altogether. Because in reality, the earlier you involve process chemistry, the more you de-risk your path forward.

The Real Cost of Waiting

In early-stage discovery, it’s easy to defer tough decisions. Speed is critical, and the focus is often on quickly accessing new compounds to drive SAR. Medicinal chemists naturally prioritize flexibility and exploration, which means rapid iteration, often on linear or patchworked synthetic routes.

But as projects move toward lead optimization, those early synthetic decisions can become expensive liabilities:

• Fragile or impractical routes
• Bottlenecks in accessing key intermediates
• High variability between batches
• Safety or environmental concerns at scale
• Delays in preparing material for preclinical studies or CDMO transfer

By the time a compound is ready to be scaled, too many teams find themselves starting over.

Start Strong: Process Chemistry as a Discovery Enabler

At Sygnature Discovery, we approach this differently.

Rather than treating process chemistry as a late-stage bolt-on, we integrate process chemists early, alongside synthetic and medicinal teams during the discovery phase. This approach doesn’t slow things down. In fact, it does the opposite.

Process chemists are expert troubleshooters. They think in terms of route efficiency, reproducibility, cost, and safety, even when working at small scale. By contributing early, they:

• Identify and simplify problematic steps before they become showstoppers
• Develop robust, scalable routes behind the scenes
• Create phase-appropriate processes that are easy to hand over or scale up
• Free up medicinal chemists to focus on what they do best: discovery

A Proven Model: Embedding Process Chemists into Discovery Teams

One of the most effective strategies we’ve implemented is embedding one or two process chemists into a 5–10 person medicinal or synthetic chemistry team.

The impact is immediate:

• Projects don’t lose momentum as they move toward candidate nomination
• Routes are built to scale without compromising speed or creativity
• Teams avoid duplicating effort across chemists working on divergent series
• Preclinical material is delivered faster and more efficiently, without last-minute surprises

This isn’t theory, it’s a model our clients have embraced. In every case where we’ve introduced this embedded approach, the teams have kept it, and expanded it.

Scale Fast: Building the Foundation for What’s Next

While CDMOs play a vital role in the clinical and commercial stages, discovery-stage chemistry still lays the groundwork. Without early process insight, CDMOs often have to reverse-engineer the route, introducing delay, rework, or even changes in regulatory filings.

By contrast, process chemists involved early can:

• Deliver fit-for-purpose material in gram-to-kilo quantities
• Generate transferable analytical packages
• Provide data that supports toxicology studies and CMC planning
• Ensure smoother, faster tech transfer with fewer surprises

This isn’t just about operational efficiency. It’s about preserving project momentum, reducing risk, and maximizing your investment in discovery.

Why It Matters Now

In an increasingly competitive R&D environment, where timelines are compressed and failure rates are unforgiving, starting with scalability in mind is a strategic advantage.

Process chemistry doesn’t need to slow down innovation. Done right, it accelerates it, and gives your molecule the best chance of success, whether you’re headed for the clinic, licensing, or partnering.e foundations are solid.

Conclusion: Don’t Wait for the CDMO to Think About Process

At Sygnature Discovery, we believe in starting strong, so you can scale fast. Process chemistry isn’t a checkpoint, it’s a catalyst. And when integrated early, it gives you the confidence to move forward faster, knowing the foundations are solid.